Diabetologia

, Volume 42, Issue 3, pp 358–364

Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients

  • F. Andreelli
  • M. Laville
  • P.-H. Ducluzeau
  • N. Vega
  • P. Vallier
  • Y. Khalfallah
  • J.-P. Riou
  • H. Vidal
Short communication

DOI: 10.1007/s001250051163

Cite this article as:
Andreelli, F., Laville, M., Ducluzeau, PH. et al. Diabetologia (1999) 42: 358. doi:10.1007/s001250051163

Summary

We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85α-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. The in vivo regulation by insulin was studied using a 3-h euglycaemic, hyperinsulinaemic clamp. There were no differences in the basal concentrations of the three mRNAs in skeletal muscle between groups. Insulin infusion produced a twofold reduction in insulin receptor substrate-1 mRNA expression in the three groups (p < 0.02). In contrast, insulin increased p85α-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects ( + 98 ± 22 % in lean and + 127 ± 16 % in obese, p < 0.02) but this effect was totally impaired in Type II diabetic patients ( + 5 ± 12 %, NS). A similar defect in insulin action on p85α-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue ( + 138 ± 25 %, p < 0.01 in lean and + 46 ± 14 %, p < 0.02 in obese and + 29 ± 11 %, NS in Type II diabetic patients). The lack of action of insulin on p85α-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. [Diabetologia (1999) 42: 358–364]

Keywords Hyperinsulinaemic clampinsulin receptorIRS-1RT-PCR.
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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • F. Andreelli
    • 1
  • M. Laville
    • 1
  • P.-H. Ducluzeau
    • 1
  • N. Vega
    • 1
  • P. Vallier
    • 1
  • Y. Khalfallah
    • 1
  • J.-P. Riou
    • 1
  • H. Vidal
    • 1
  1. 1.INSERM U.449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine R. T. H. Laënnec, and Service d'Endocrinologie Diabétologie et Nutrition, Hopital E. Herriot, Lyon, FranceFR